Bcl-2 leads to expression of anti-DNA B cells but no nephritis: a model for a clinical subset

Eur J Immunol. 1999 Oct;29(10):3168-78. doi: 10.1002/(SICI)1521-4141(199910)29:10<3168::AID-IMMU3168>3.0.CO;2-H.


Transgenic mice expressing anti-DNA antibodies have been extensively studied as a model for understanding B cell regulation in systemic lupus erythematosus (SLE). BALB/c mice transgenic for the R4A-gamma2b heavy chain of an anti-double-stranded DNA (dsDNA) antibody produce two populations of high-affinity anti-dsDNA B cells, one deleted, and the other anergized. We generated double-transgenic BALB / c mice expressing both the R4A-gamma2b heavy chain and the anti-apoptotic bcl-2 gene in the B cell compartment to study whether bcl-2 overexpression differentially affected anergic and deleted B cells. The double-transgenic mice (R4A/bcl-2) express elevated serum titers of both high- and low-affinity anti-dsDNA antibodies and display rescue of autoreactive B cells that are normally either deleted or anergized. Despite the presence of anti-dsDNA antibodies in their serum, R4A/bcl-2-transgenic mice do not develop nephritis, demonstrating that overexpression of bcl-2 is not by itself sufficient to allow disease progression. This phenotype resembles that of some SLE patients who have high titers of anti-DNA antibodies without nephritis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibody Affinity / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Disease Models, Animal
  • Genes, Immunoglobulin
  • Hybridomas / immunology
  • Hybridomas / metabolism
  • Immunoglobulin Heavy Chains / biosynthesis
  • Immunoglobulin Light Chains / biosynthesis
  • Lupus Erythematosus, Systemic / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nephritis / etiology
  • Nephritis / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Spleen / immunology


  • Antibodies, Antinuclear
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Proto-Oncogene Proteins c-bcl-2